Pathophysiology

CF is a disease of exocrine gland epithelial cells where CFTR expression is prevalent. Normally, these cells transport chloride through CFTR chloride channels with sodium and water accompanying this flux across the cell membrane (Fig. 16-1). CFTR is regulated by protein kinases in response to varying levels of the intracellular second messenger cyclic-3',5'-adenosine monophosphate (cAMP). CFTR also downregulates the epithelial sodium channel, regulates calcium-activated chloride and potassium channels, and may function in exocytosis and formation of plasma membrane molecular complexes and proteins important in inflammatory responses.2 In CF, the CFTR chloride channel is dysfunctional and usually results in decreased chloride secretion and increased sodium absorption, leading to altered viscosity of fluid excreted by the exocrine glands and mucosal obstruction.

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